Endocrine Abstracts

The orphan nuclear receptor, SF-1, is sumoylated in adrenal and gonadal tissues, but the role of sumoylation in pituitary gonadotrophs is currently unknown. We performed expression studies for key components of sumoylation machinery in αT3-1 and LβT2 gonadotroph cell lines, using RT-PCR. Expression of the genes encoding the SUMO proteins (Sumo1, Sumo2, Sumo3) as well as the E3 ligase enzymes responsible for their covalent linkage (Pias1, Pias2/xα, Pias...

Background: Multiple sclerosis (MS) is associated with low ambient ultraviolet B (UVB) light in childhood and in utero (relative risk of developing MS is 1.2 for those born in spring). Besides, the MS-linked HLA-DRB1 allele interacts strongly with vitamin D in vitro, and vitamin D levels are lower in MS patients. Fatigue and musculoskeletal aches/pains are prominent symptoms in both MS and vitamin D deficiency. Moreover, having any chronic disease may predispose to stay...

Background: The development of recombinant biologics such as interferon, insulin and Growth Hormone (GH) has had a major impact on the management of diseases including hepatitis, diabetes and GH-deficiency. However, most biologics undergo rapid renal filtration and proteolytic degradation, necessitating frequent dosing regimens. Pegylation can successfully delay clearance but has several drawbacks including potential toxicity, expense and reduced activity. There is therefore n...

Background: Leptin is an important regulator of the immune response. Therapeutics that modulate leptin signalling are considered to be a potential targets in a number of immune related conditions. The role of leptin antagonists to suppress the immune system, slowing the progression of autoimmune diseases is a widely discussed idea. However, leptin agonists may also be useful to up-regulate the immune response during malnutrition. The aim of this project was to develop long-las...

Introduction: RAMPs (receptor activity-modifying proteins) are single-pass transmembrane accessory proteins required for appropriate signalling of the G-protein coupled receptors; CRLR (Calcitonin receptor like receptor) and CTR (Calcitonin receptor). There are three forms of human RAMPs known as, RAMP1, 2 and 3. RAMP3 heterodimerises with CRLR or CTR to form a high affinity receptor for the peptide hormones adrenomedullin and amylin, respectively. However, the exact mechanism...

Background: Leptin has multiple functions including modulating energy homeostasis and the immune response. Leptin is an important target for therapy to modulate the immune response in several autoimmune diseases. Although the structure of leptin is known, that of its receptor remains unsolved. The aim of this project was to express and purify the extracellular domain the leptin receptor (ObR) in order to carry out functional and crystallisation studies to elucidate the mechani...

Introduction: The growth hormone receptor (GHR) consists of 620 residues and belongs to the class I cytokine receptor family. It is a single membrane spanning protein that binds its ligand, GH, via the extracellular domain. GH binding to GHR induces a conformational change in the preformed receptor dimer, which leads to intracellular signalling. Correct functional dimerisation of two GHR molecules is essential for GH signalling. We have previously shown that membrane bound tru...

We have shown that linked polymorphisms in the aldosterone synthase gene (CYP11B2) are associated with hypertension and altered aldosterone production. However, the most consistent intermediate phenotype associated with this genetic variation is increased plasma 11-deoxycortisol (S) and urinary excretion of its metabolite, tetrahydrodeoxycortisol (THS); this is paradoxical as S is a substrate for the enzyme 11beta-hydroxylase, encoded by the neighbouring gene, CYP11B1. However...

Endothelial dysfunction (ED) is common in type 2 diabetes mellitus (T2DM) and can lead to microvascular and macrovascular complications. The aim of our study was to assess ED in patients with T2DM (n=21; 13 with diabetic neuropathy (DN), 8 without DN) and compare them with non-diabetic controls (n=10).Methods: ED was assessed by skin microcirculation (SM) and biochemical markers (BM) of endothelial function. SM was measured on the dorsu...

Type 2 diabetes mellitus (T2DM) and obesity are linked to osteoporosis, making these patients at increased risk of developing fractures. In this study we aimed to investigate bone biochemical markers and bone structure in diabetic patients to compare with non-diabetic controls.Methods: We recruited 21 type 2 diabetic patients and 10 non-diabetic controls. Fasting blood samples were collected for markers of bone turnover (Sclerostin (SCL), RANKL, OPG, OPN...